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    Mutant mouse lacking the expression of interferon regulatory factor 1 (IRF-1)
    5.
    发明授权
    Mutant mouse lacking the expression of interferon regulatory factor 1 (IRF-1) 失效
    缺乏干扰素调节因子1（IRF-1）表达的突变体小鼠

    公开(公告)号：US5731490A

    公开(公告)日：1998-03-24

    申请号：US392292

    申请日：1995-02-21

    申请人： Tak W. Mak ,  Tadatsugu Taniguchi

    发明人： Tak W. Mak ,  Tadatsugu Taniguchi

    IPC分类号： C07K14/47 ,  C12N15/85 ,  C12N15/00 ,  C12N5/10 ,  C12N15/87 ,  C12N15/90

    CPC分类号： C12N15/8509 ,  A01K67/0276 ,  C07K14/4702 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03

    摘要： Interferon regulatory factor-1 (IRF-1) is implicated in the regulation of type I interferons (IFN) and cell growth. The invention is a mutant mouse lacking expression of the IRF-1 gene. Mice lacking IRF-1 did not differ from normal mice in size, behaviour, or reproductive ability. With fibroblasts derived from these mutant mice, it was shown that type I IFN induction is dramatically reduced when cells are induced by poly(I):poly(C). In contrast, no differences were found when cells are induced by New Castle Disease Virus (NDV), or induced by poly(I):poly(C) with prior treatment of IFN-.beta.. On the other hand, the induction levels of IFN-inducible genes such as MHC class I and 2'-5' oligoadenylate synthetase (2'5'OAS) were not affected. Collectively, these results illustrate an IRF-1 independent mechanism of gene induction for type I IFN and these IFN-inducible genes. The critical role of IRF-1 in the immune system has been documented for the first time by the observation that the number of TcR.alpha..beta..sup.+ CD4.sup.- CD8.sup.+ T cells were dramatically reduced in IRF-1 deficient mice. This phenotype may be ascribed to a thymocyte developmental defect between the double positive and single positive stages during CD8.sup.+ T cell ontogeny.

    摘要翻译： 干扰素调节因子-1（IRF-1）涉及I型干扰素（IFN）和细胞生长的调节。 本发明是缺少IRF-1基因表达的突变体小鼠。 缺乏IRF-1的小鼠与正常小鼠的大小，行为或生殖能力没有差异。 使用衍生自这些突变小鼠的成纤维细胞，显示当通过聚（I）：聚（C）诱导细胞时，I型IFN诱导显着降低。 相比之下，当新城堡病毒（NDV）诱导细胞或由poly（I）：poly（C））诱导IFN-β之前没有发现差异。 另一方面，IFN-诱导型基因如MHC I类和2'-5'寡腺苷酸合成酶（2'5'OAS）的诱导水平不受影响。 总而言之，这些结果说明了I型IFN和这些IFN诱导型基因的基因诱导的IRF-1独立机制。 IRF-1在免疫系统中的关键作用已经首次记录在IRF-1缺陷小鼠中，TcRαβ+ CD4-CD8 + T细胞数量急剧减少。 这种表型可能归因于CD8 + T细胞个体发育期间双阳性和单阳性阶段之间的胸腺细胞发育缺陷。

    Inhibitor of HMGB Protein-Mediated Immune Response Activation, and Screening Method
    7.
    发明申请
    Inhibitor of HMGB Protein-Mediated Immune Response Activation, and Screening Method 有权
    HMGB蛋白介导的免疫反应激活抑制剂和筛选方法

    公开(公告)号：US20130183348A1

    公开(公告)日：2013-07-18

    申请号：US13823913

    申请日：2011-09-14

    申请人： Tadatsugu Taniguchi ,  Hideyuki Yanai

    发明人： Tadatsugu Taniguchi ,  Hideyuki Yanai

    IPC分类号： A61K31/7088

    CPC分类号： A61K31/7088 ,  A61K31/7125 ,  C12N15/113 ,  C12N15/117 ,  C12N2310/14 ,  C12N2310/17 ,  C12N2310/315 ,  G01N33/6875 ,  G01N2333/4703 ,  G01N2500/02

    摘要： Provided are an inhibitor of activation of an immune response mediated by an HMGB protein, the inhibitor containing at least one compound selected from the group consisting of a phosphorothioate oligonucleotide and a derivative thereof, and a method of screening for an inhibitor or enhancer of activation of an immune response mediated by an HMGB protein, the method including a mixing step of mixing an HMGB protein and a labeled nucleic acid in the presence and absence of a test substance; a quantifying step of quantifying the HMGB protein bound to the labeled nucleic acid; and a determination step of determining that the test substance is an inhibitor of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is less than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance and determining that the test substance is an enhancer of activation of an immune response mediated by the HMGB protein when the amount of the HMGB protein bound to the labeled nucleic acid in the presence of the test substance is higher than the amount of the HMGB protein bound to the labeled nucleic acid in the absence of the test substance.

    摘要翻译： 提供了由HMGB蛋白质介导的免疫应答的活化抑制剂，所述抑制剂含有至少一种选自硫代磷酸酯寡核苷酸及其衍生物的化合物，以及筛选抑制剂或增强剂的活化的方法 由HMGB蛋白介导的免疫应答，所述方法包括在存在和不存在测试物质的情况下混合HMGB蛋白和标记的核酸的混合步骤; 量化与标记核酸结合的HMGB蛋白质的量化步骤; 以及确定步骤，当在所述测试物质存在下与所述标记的核酸结合的HMGB蛋白质的量小于所述测试物质的量时，所述测定物质是由所述HMGB蛋白质介导的免疫应答的活化抑制剂 HMGB蛋白在不存在测试物质的情况下与标记的核酸结合，并确定当HMGB蛋白与标记的核酸结合的量的HMGB蛋白的量结合时，测试物质是激活HMGB蛋白介导的免疫应答的增强剂 测试物质的存在高于在不存在测试物质的情况下与标记的核酸结合的HMGB蛋白质的量。